Neural Pharm Podcast

References: Psychedelics legislation in Colorado Springs: https://gazette.com/health/fountain-joins-colorado-springs-in-seeking-to-regulate-fledgling-psychedelic-mushroom-industry/article_22a66456-a1da-11ef-a515-57588c741084.htmlOregon Psilocybin Ballot Measure Results: https://www.opb.org/article/2024/11/07/psilocybin-ban-mushroom-hallucinogenic-ballot-politics-elections-oregon/Vermont Psychedelic Working Group Final Report: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://legislature.vermont.gov/assets/Legislative-Reports/The-Psychedelic-Therapy-Advisory-Working-Group_Final-Report.pdfUS Life Expectancy Expected to Decline to 66th Globally by 2050: https://www.healthdata.org/news-events/newsroom/news-releases/increases-us-life-expectancy-forecasted-stall-2050-poorer-health#:~:text=Life%20expectancy%20in%20the%20US,2022%20to%2066th%20in%202050United Healthcare uses faulty AI to deny claims: https://www.cbsnews.com/news/unitedhealth-lawsuit-ai-deny-claims-medicare-advantage-health-insurance-denials/DEA Funding chart: https://crsreports.congress.gov/product/pdf/R/R44576See here also, Why is the FDA funded by the companies it regulates?: https://today.uconn.edu/2021/05/why-is-the-fda-funded-in-part-by-the-companies-it-regulates-2/Other references to topics discussed on this edition of podcast:See Colby’s previous article on Measure 110 in Oregon—which decriminalized nearly all categories of drugs, and has since been overturned: Right to Try bill articles (since this was discussed on this edition of podcast): Trump gave patients “Right to Try” but it hasn’t helped them: https://www.statnews.com/2024/08/02/trump-gave-patients-right-to-try-it-hasnt-helped-them/DEA says Right to Try doesn’t include substances listed as Schedule I: https://www.marijuanamoment.net/in-case-on-psilocybin-access-for-cancer-patients-dea-says-federal-right-to-try-law-does-not-provide-any-exemptions-from-controlled-substance-act/Understanding the Right to Try act: https://pmc.ncbi.nlm.nih.gov/articles/PMC7416898/ Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Show notes and references:* Please note: This was recorded prior to the election on Nov 5. We will discuss the results and predictions for the future of healthcare policy in America in our next edition.”Kanna references: Bennett, A. C., et al. "Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action." Journal of physiology and biochemistry 74.4 (2018): 539-547.Chiu, Simon, et al. "Proof-of-concept randomized controlled study of cognition effects of the proprietary extract Sceletium tortuosum (Zembrin) targeting phosphodiesterase-4 in cognitively healthy subjects: implications for Alzheimer’s dementia." Evidence-Based Complementary and Alternative Medicine 2014 (2014).Chiu, S., et al. "Exploring Standardized Zembrin® Extracts from the South African plant Sceletium tortuosum in Dual Targeting Phosphodiesterase-4 (PDE-4) and Serotonin Reuptake Inhibition as potential treatment in Schizophrenia." Int J Complement Alt Med 6.5 (2017): 00203.Coetzee, Dirk D., Víctor López, and Carine Smith. "High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor." Journal of Ethnopharmacology 177 (2016): 111-116.Gericke, N., and Alvaro M. Viljoen. "Sceletium—a review update." Journal of Ethnopharmacology 119.3 (2008): 653-663.Gericke, Johané. Evaluating the antidepressant-like properties of Sceletium tortuosum, alone and as adjunctive treatment. Diss. North-West University (South-Africa), 2020.Louw, Letitia. Investigation into potential endocrine disruptive effects of Sceletium tortuosum. Diss. Stellenbosch: Stellenbosch University, 2018.Reay, Jonathon, et al. "Sceletium tortuosum (Zembrin®) ameliorates experimentally induced anxiety in healthy volunteers." Human Psychopharmacology: Clinical and Experimental 35.6 (2020): 1-7.Reay J., Wetherell M.A., Morton E., Lillis J., Badmaev V. Sceletium tortuosum (Zembrin®) ameliorates experimentally induced anxiety in healthy volunteers. Hum. Psychopharmacol. Clin. Exp. 2020;35:1–7. doi: 10.1002/hup.2753. [PubMed] [CrossRef] [Google Scholar]    https://pubmed.ncbi.nlm.nih.gov/32761980/Schell R. Bachelor’s Thesis. Scripps Colleges; Claremont, CA, USA: 2014. Sceletium tortuosum and Mesembrine: A Potential Alternative Treatment for Depression. [Google Scholar] [Ref list]    Terburg, David, et al. "Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus." Neuropsychopharmacology 38.13 (2013): 2708-2716.Van der Walt, S. Development and evaluation of a medicated chewing gum containing Sceletium tortuosum. Diss. North-West University, 2018.Villarreal M.L., Sharma A., Cardoso-Taketa A., Garcia G. A systematic updated review of scientifically tested selected plants used for anxiety disorders. Bot. Targets. 2012;2:21–39. doi: 10.2147/BTAT.S20593. [CrossRef] [Google Scholar]https://www.tandfonline.com/doi/abs/10.2147/BTAT.S20593For more detailed information on kanna's safety and how to avoid withdrawals: All You Need to Know About Kanna's Safety, Risks, and WithdrawalsPsychedelics Today interview with Rick Doblin (Ph.D.), founder of MAPS, cited in the podcast: https://psychedelicstoday.com/2024/10/15/the-fda-mdma-and-public-perception-was-the-fda-fair-to-lykos/ October 15 2024. Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

**Note this was recorded the first week of July before President Biden announced he would not run for re-election. I know that feels like a lifetime ago but just jump in your time machine for a bit at the beginning of the podcast please. We will likely start our next episode on the pharmacology of Kanna with a “catch up” on Kamala Harris v Trump**Footnotes, References and corrections:See below to watch the live stream of the FDA advisory panel decision on MDMA Assisted Therapy; a review of the MAPP1 and MAPP2 trial data: To review the MAPP1 and MAPP2 trials, listen to our first episode hereTo read about how the FDA is funded, and what “user fees” are hereTo read the open letter from the Heroic Hearts Project (referenced by Chris) on the FDA advisory panel’s decision on veterans mental health, click on this link: To read a bipartisan letter to President Biden in support of MDMA assisted therapy, click hereTo listen to an interview in Psychedelics Today referenced by Colby in the podcast with Dr. Amanda Holley, a regulatory consultant and pharmacologist in non-clinical drug development, click here. To read about GLP1 compounding regulations, and how big pharma is lying about owning exclusivity to semaglutide and tirzepatide, click here for a statement from the Alliance for Pharmacy Compounding.FACT CHECKS—Colby erroneously said the FDA advisory panel reviewed only phase 2 trial data from Lykos; in reality it was phase 3 data from the MAPP1 and MAPP2 trials—ICER, which is referenced several times in the episode stands for the Institute for Clinical and Economic Review, an organization that discusses the pharmacoeconomic utility of pharmaceutical therapies. Chris claimed they were mostly funded by user fees from manufacturers, similar to the FDA, but ICER claims they receive most funding from non-profit sources, with only 14% from manufacturers. To read more about ICER’s letter in regards to MDMA assisted therapy, review my previous article on the topic here. (Note the Heroic Hearts project uncovered ICER’s potential conflicts of interest not known to me at the time of this publication). —Not necessarily a fact check, as at the time we recorded our information was correct, but as news moves quickly it has been revealed through toxicology testing that some Diamond Shruumz products do contain psilocybin despite the manufacturers claims they don’t. The FDA possibly didn’t know this either at the time of their original publication. To our listeners, please do not consume any products from this brand, as they have already been associated with 113 illnesses and 2 deaths nationwide. Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

For more information on Shuna’s work visit: https://www.shunamorelli.com/ Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

**To learn more about Danielle and the services she provides, go to the Microdosing Humboldt website: https://www.microdosinghumboldt.com/home or follow her on Instagram at: https://www.instagram.com/microdosinghumboldt/ ** Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Thanks for reading Neural Pharm! Subscribe for free to receive new posts and support my work.References:Cassels B, et al. Dark classics in chemical neuroscience: mescaline. ACS Publications. 9 Sept 2018. https://pubs.acs.org/doi/10.1021/acschemneuro.8b00215Dinis-Oliveira RJ, et al. Pharmacokinetic and pharmacodynamic aspects of peyote and mescaline: clinical and forensic repercussions. 1 Aug 2019. Current Molecular Pharmacology.https://www.ingentaconnect.com/contentone/ben/cmp/2019/00000012/00000003/art00003Engel L, et al. Mescaline, peyote, and San Pedro: is sustainability important for cacti consumers? 18 Aug 2023. Journal of Psychedelic Studies. https://akjournals.com/view/journals/2054/7/2/article-p135.xmlJay M. A Century of mescaline. Chacruna. 30 April 2021. https://chacruna.net/century_of_mescaline/Kolaczynska K, et al. Receptor interaction profiles of 4-alkoxy-3,5-dimethoxy-phenylethylamines (mescaline derivatives) and related amphetamines. Frontiers in Pharmacology. 8 Feb 2022. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.794254/fullPollan, Michael. This is Your Mind on Plants. 2021. Penguin Press. New York. Uthang MV, et al. The epidemiology of mescaline use: pattern for use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects. 5 May 2021. British Association for Psychopharmacology. https://journals.sagepub.com/doi/full/10.1177/02698811211013583 Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Thanks for reading Neural Pharm! Subscribe for free to receive new posts and support my work.Footnotes:—Yes I will acknowledge that I mispronounced “anecdotal” a few times during this interview. For some reason this is always one of those tricky words for me to say, and even past Presidents and Presidential candidates have mispronounced words from time to time. If you want to roast me for it (politely) feel free to leave a comment.—For reference to the article that Ben Malcolm mentioned in the interview about Ketamine being non-inferior to Electro-Convulsive Therapy (ECT), please see the following article: Anand A, et al. Ketamine vs ECT for Non-Psychotic Treatment Resistant Major Depression. NEJM. 2023; 388: 2315-2325. https://www.nejm.org/doi/10.1056/NEJMoa2302399In summary: This study analyzed 405 patients aged 21 to 75 years old with treatment resistant major depression, and randomized patients to either ketamine or ECT. Patients received 0.5 mg/kg twice a week or ECT three times a week over a three week treatment period, and found a response rate of 55% for ketamine vs 41% for ECT. As ECT has often been considered the “gold standard” for resistant depression, this was a major finding. We did not cover this on our previous Ketamine episode but you can listen here for review of this episode. Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Thanks for reading Neural Pharm! Subscribe for free to receive new posts and support my work.References:Arrone L, et al. Continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity: the SURMOUNT-4 Randomized Clinical Trial. JAMA. 11 Dec 2023. https://jamanetwork.com/journals/jama/fullarticle/2812936Attia P and Gifford B. Outlive: The Science & Art of Longevity First edition., Harmony, 2023. Bliss M. The History of a Wonderful Thing We Call Insulin. American Diabetes Association. 1 July 2019. https://diabetes.org/blog/history-wonderful-thing-we-call-insulinHendershot C. Use of GLP-1 Receptor Agonists to Treat Substance and Alcohol Use. University of North Carolina. 5 Dec 2023. https://news.unchealthcare.org/2023/12/use-of-glp-1-receptor-agonists-to-treat-substance-and-alcohol-use-disorders-is-promising-but-premature/. Jay M. Walmart says users of weight loss drug are buying less food. NBC News. 5 Nov 2023. https://www.nbcnews.com/business/consumer/ozempic-drug-users-are-buying-less-food-walmart-says-rcna119000Klausen M, et al. The Role of Glucagon Like 1 Peptide (GLP-1) in Addictive Disorders. British Journal of Pharmacology. Feb. 2022. https://pubmed.ncbi.nlm.nih.gov/34532853/Leslie M. Hot Weight Loss Drugs Tested Against Addiction. Science. Sept 2023. https://www.science.org/content/article/hot-weight-loss-drugs-tested-addiction-treatmentsLingvay I, et al. Efficacy and Safety of Once Weekly Semaglutide versus daily Canagliflozin as add-on to Metformin in Patients with Type 2 Diabetes (SUSTAIN 8)…The Lancet. Nov 2019. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30311-0/fulltextMansour N, et al. Effects of Early Adjunctive Pharmacotherapy on Serum Levels of Brain Injury Biomarkers in Patients with Traumatic Brain Injury: A Systematic Review of Randomized Controlled Studies. Frontiers in Pharmacology. 4 May 2023. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1185277/full Mckenzie H. GLP-1 Drugs Show Promise in Alcohol, Opioid Use Disorders. Biospace. 3 Aug 2023. https://www.biospace.com/article/glp-1-drugs-show-promise-in-alcohol-opioid-use-disorders-/. Quianzon C, et al. History of Current Non-Insulin Medications for Diabetes Mellitus. Journal of Community Hospital: Internal Medicine Perspectives. 15 Oct 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/Reger M, et al. Tramautic Brain Injury and Veteran Mortality After the War in Afghanistan. JAMA. 11 Feb 2022. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788981#:~:text=Estimates%20suggest%20that%20between%209,service%20members%20experienced%20a%20TBI.&text=Complicating%20matters%20further%2C%20many%20veterans,the%20worst%20lifetime%20injury%20sustainedShevchouck O, at al. An Overview of Appetite-Regulatory Peptides in Addiction Processes: From Bench to Bed Side. Frontiers in Neuroscience. 8 Dec 2021. https://www.frontiersin.org/articles/10.3389/fnins.2021.774050/ful Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Ibogaine References:Alper K, et al. Ibogaine: Scientific Literature Overview. International Center for Ethnobotanical Education. 2012. Available at: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.iceers.org/Documents_ICEERS_site/Scientific_Papers/ibogaine/ICEERS2012_Ibogaine_literature_compilation.pdfCorkery JM. Ibogaine as a Treatment for Substance Misuse: Potential Benefits and Practical Dangers. Progress in Brain Research. 2018(242); 217-257. https://www.sciencedirect.com/science/article/abs/pii/S0079612318300979?via%3DihubDalton C. A Detox Drug Promises Miracles if it Doesn’t Kill You First. Wired. 15 Sept 2019. https://www.wired.com/story/a-detox-drug-promises-miraclesif-it-doesnt-kill-you-first/Davis AK, et al. Subjective Effectiveness of Ibogaine Treatment for Problematic Opioid Consumption: Short and Long Term Outcomes and Current Psychological Functioning. Journal of Psychedelic Studies. 2017. https://akjournals.com/view/journals/2054/1/2/article-p65.xmlKock P, et al. A Systematic Literature Review of Clinical Trials and Therapeutic Applications of Ibogaine. Journal of Substance Abuse Treatment. 2022. https://www.sciencedirect.com/science/article/pii/S0740547221004438Mash D. Breaking the Cycle of Opioid Use Disorder. Multi-Disciplinary Association of Psychedelic Studies convention. Presented 22 June 2023. Accessed 17 Dec 2023. Mash D, et al. Ibogaine Detoxification Transitions Opioid and Cocaine Users between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology. 2018. https://www.frontiersin.org/articles/10.3389/fphar.2018.00529/fullMash D and Luz M. Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse. Drug Metabolism and Toxicology. 2021. https://www.tandfonline.com/doi/full/10.1080/17425255.2021.1944099Oaklander M. Inside Ibogaine: One of the most Promising and Perilous Psychedelics for Addiction. Time Magazine. 5 April 2021. https://time.com/5951772/ibogaine-drug-treatment-addiction/Popik P, et al. Pharmacology of Ibogaine and Ibogaine Related Alkaloids. Progress in Brain Research. 2018. Siebert A. Kentucky Summit to Explore Ibogaine Treatment for Opioid Use Disorder. Forbes. 17 Nov 2023. https://www.forbes.com/sites/amandasiebert/2023/11/17/kentucky-summit-to-explore-ibogaine-treatment-for-opioid-use-disorder/GLP-1 references (discussed in intro):Could Obesity Drugs Take a Bite out of the Food Industry? Morgan Stanley. 5 Sept 2023. https://www.morganstanley.com/ideas/obesity-drugs-food-industryLilly’s Zepbound Achieved Additional 6.7% Weight Loss….[press release]. Associated Press. 11 Dec 2023. Thompson D. The Weight Loss Drug Revolution Part 1. Plain English [podcast], The Ringer podcast network. Aired 12 Dec 2023. Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Footnotes:For more on how to help our nation’s veterans:https://www.va.gov/REACH/ Veteran crisis line: Dial 988 and press 1. Or text 838255. Seasonal Affectiveness Disorder. National Institute of Mental Health. https://www.nimh.nih.gov/health/publications/seasonal-affective-disorderKentucky Ibogaine Initiative: https://www.kentuckyibogaineinitiative.com/Huberman, Andrew. Mental Health Toolkit: Tools to bolster your mood and mental health. Huberman Lab [podcast]. 30 Oct 2023References on Kratom: FDA and Kratom. https://www.fda.gov/news-events/public-health-focus/fda-and-kratom. 21 July 2023. Gandhi D, et al. Kratom induced severe cholestatic liver injury histologically mimicking primary biliary cholangitis: a case report. World Journal of Hepatology. 27 Oct 2020; 12(10): 863-869. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643221/Gianutsos G. The DEA Changes its mind on Kratom. https://www.uspharmacist.com/article/the-dea-changes-its-mind-on-kratom#:~:text=In%20making%20this%20determination%20on,safety%20for%20use%20under%20medical. US Pharmacist. 17 March 2017Happy Hippo. https://happyhippo.com/blogs/kratom-blog/the-benefits-of-agmatine-sulfate-as-a-kratom-potentiatorJentsch MJ, Pippin MM. Kratom. Stat Pearls. 28 August 2023. https://www.ncbi.nlm.nih.gov/books/NBK585120/Kratom. Natural Medicines Comprehensive Database. Updated 6 June 2023.Kratom. California Poison Control System. 22 June 2016. Rexer B. Is Kratom legal? Kratom legality by state. Sprout Health Group. https://www.sprouthealthgroup.com/substances/is-kratom-legal-by-state/Settle A and Yang C. A Case of Severe Kratom Addiction Contributing to a Suicide Attempt. Cureus. 2022 Sept; 14(9): e29698. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616552/Ya K, et al. Pharmacokinetics of mitragynine, a major analgesic alkaloid in kratom: a systematic review. 2019(43): 73-82. https://www.sciencedirect.com/science/article/abs/pii/S1876201819302114 Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

*For listeners in the Seattle/Tacoma/Bellevue area: Mention this podcast and receive 10% off an initial ketamine treatment series at NW Ketamine Clinic For more information go to: https://nwketamineclinics.com/ Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Foot notes: UK article on Psilocybin therapy cost effectiveness:McCrone P, et al. Cost effectiveness of psilocybin assisted therapy for severe depression: exploratory findings from a decision analytic model. Psychological Medicine. 2 June 2023. https://www.cambridge.org/core/journals/psychological-medicine/article/costeffectiveness-of-psilocybinassisted-therapy-for-severe-depression-exploratory-findings-from-a-decision-analytic-model/8594CAC2F8D60F8C7B9A1CE3C3195B74MDMA Assisted Therapy for Social Anxiety Disorder—Phase II trial being conducted at Portland (OR) Psychotherapy, link here for those interested in finding out more information or enrolling: https://portlandmdmatherapy.com/participate/Krane, K. HHS Call to reschedule marijuana is a big deal: here’s why. Forbes. 31 Aug 2023. https://www.forbes.com/sites/kriskrane/2023/08/31/hhs-call-to-reschedule-marijuana-is-a-big-deal-heres-why/?sh=af122092a4a7Beasley M, et al. Poisoning due to tutin in honey—a report of an outbreak in New Zealand. The New Zealand Medical Journal. 2018; 131(1473): 59-71. https://pubmed.ncbi.nlm.nih.gov/29649198/Bryce E. The Strange History of Mad Honey. Modern Farmer. 2014. https://modernfarmer.com/2014/09/strange-history-hallucinogenic-mad-honey/Honey. Natural Medicines comprehensive database. Last updated 12 June 2023. Accessed 15 Oct 2023.How eating “Mad Honey” cost Pompey the Great 1000 soldiers. Texas A&M Research. 3 Nov 2014. https://research.tamu.edu/2014/11/03/how-eating-mad-honey-cost-pompey-the-great-1000-soldiers/ Jansen S, et al. Grayanotoxin poisoning: mad honey disease and beyond. Cardiovascular Toxicology. 2012; 12(3): 208-215. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404272/Johnson S. “Mad Honey: the rare hallucinogen from the mountains of Nepal. Big Think. 26 Dec 2022. https://bigthink.com/health/mad-honey/Ozhan H, et al. Cardiac emergencies caused by honey ingestion: a single centre experience. Emergency Medicine Journal. 2004; 21(6:) 742-744. https://pubmed.ncbi.nlm.nih.gov/15496712/Ullah S, et al. Mad Honey: uses, intoxicating/poisoning effects, diagnosis, and treatment. RSC Advances. 2018; 8(33): 18635-18646. For those interested in learning more about the use of Mad Honey in warfare, check out this podcast at Ridiculous History: Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Footnotes:To find out more on Psyched Wellness, or to order Calm to have it shipped to home, click on the link here: For more on Amanita Muscaria, please view the article I published on my Substack by clicking the link here Wired article on microdosing: https://www.wired.co.uk/article/microdosing-workplace-shroom-boom#intcid=_wired-uk-bottom-recirc_397cdbf7-d656-4f04-b4a2-111a2dd3ef9f_entity-topic-similarity-Microdosing Amanita for neuropathic pain: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614567/*Be on the lookout for an affiliate link to purchase “Calm” extract in the coming days* Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

***Please take a couple minutes to complete a brief survey about the podcast here. If you have any specific open ended feedback for the podcast, please feel free to leave a comment below or email at [email protected]*** References: “Ayahuasca and 5 Me-ODMT.” UC Berkeley Center for the Science of Psychedelics. Last accessed 28 Sept 2023. https://psychedelics.berkeley.edu/substance/ayahuasca/Bernal A, et al. Reactivations after 5-methoxy-N,N-dimethyltryptamine use in naturalistic settings: an initial exploratory analysis of the phenomenon’s predictors and its emotional valence. Frontiers in Psychiatry. 2022; 13: 1049643Halberstadt A. Dimethyltryptamine: Possible Endogenous Ligand of the Sigma-1 Receptor. MAPS bulletin: Spring 2011 volume 21, number 1. https://maps.org/wp-content/uploads/2021/08/v21n1-56to58-1.pdfNiznansky L, et al. Ayahuasca as a Decoction Applied to Human: Analytical Methods, Pharmacology, and Potential Toxic Effects. Journal of Clinical Medicine. 2022; 11(4): 1147. https://www.mdpi.com/2077-0383/11/4/1147Paredes R. DMT vs Ayahuasca: is one better than the other? Mind Better. 17 Aug 2022. https://mindbetter.com/dmt-vs-ayahuasca/Reckweg J, et al. A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy N,N-dimethyltryptamine formulation (GH001) in patients with treatment resistant depression. Frontiers in Psychiatry. 2023; 14: 1133414. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319409/Smith, Patrick. Ayahuasca vs DMT. Third Wave. 30 April 2023 (accessed 28 Sept 2023). https://thethirdwave.co/ayahuasca-vs-dmt/Thomas, SS. Ayahuasa vs DMT: Unveiling the Differences and Similarities. Psychable. 23 April 2021. https://psychable.com/ayahuasca/ayahuasca-vs-dmt-whats-the-difference Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

References:Article referenced in the beginning:Martinez-Marmol, et al. Hericerin derivatives activates a pan neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spacial memory. Journal of Neurochemistry. 2023(165);6: 791-808Ballard E and Zarate C. The role of disassociation in ketamine’s anti-depressant effects. Nature Communications. 2020: 6431Bobo WV, et al. Ketamine for treatment resistant unipolar and bipolar major depression: Critical review and implications for clinical practice. Depression and Anxiety. 6 April 2016.Esketamine [package insert]. Janssen Neuroscience. July 2023. Fava M, et al. Double blind, placebo controlled dose ranging trial of intravenous ketamine as adjunctive therapy in treatment resistant depression (TRD). Molecular Psychiatry. 2020(25): 1592-1603Gales A, Maxwell S. Ketamine: recent evidence and clinical uses. World Federation of Societies of Anesthesiologists. 12 June 2018. Johnston JN, et al. Ketamine in neuropsychiatric disorders: an update. Neuropsychopharmacology. 2023Loo CK, et al. Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular, and subcutaneous routes for ketamine in depression. Acta Psychiatria Scandinavica. 30 March 2016. Mandal S, et al. Efficacy of Ketamine therapy in the treatment of depression. Indian Journal of Psychiatry. 2019 Sept-Oct; 61(5). VA/DoD Clinical Practice Guideline. (2022). The Management of Major Depressive Disorder. Washington, DC: U.S. Government Printing Office. Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

References: Cheung T. COMPASS Announces Positive Outcome of 25 mg COMP360 Psilocybin Therapy as Adjunct to SSRI Anti-depressant in Open-Label, Treatment-Resistant Depression Study. COMPASS Health. 13 Dec 2021 [press release]. Grinspoon P. The Popularity of Microdosing of Psychedelics: What Does the Science Say? Harvard Health. 19 Sept 2022. Gukasyan N, et al. Attenuation of Psilocybin Mushroom Effects During and After SSRI/SNRI Anti-depressant Use. Sage Journals. 2023 Jul; 37(7): 707-716Malcolm B and Thomas K. Serotonin Toxicity of Serotonergic Psychedelics. Psychopharmacology. 2022;239: 1881-1891Perez E, et al. The Psilocybin-Blunting Effects of SSRIs and Anti-depressants. Psychedelic Passage. 3 June 2022. Raison C, et al. Single Dose Psilocybin for Major Depressive Disorder. JAMA. 2023; 330(9): 843-853 Drug Interaction tables for reference:Microdosing mom article mentioned in podcast: https://psychedelicspotlight.com/indiana-nurse-faces-ten-years-in-prison-for-microdosing-psilocybin-mushrooms/ Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

References:Structural comparison of DMT, psilocin, and serotonin. Adkins A and Ferguson MC. “Research update: MDMA and psilocybin for pain management.” Practical Pain Management. 18 June 2022. https://www.practicalpainmanagement.com/news/research-update-mdma-and-psilocybin-for-pain-management. Accessed 30 July 2023Bornemann J, et al. “Self-medication for chronic pain using class psychedelics: A qualitative investigation to inform future research.” Frontiers in Psychiatry. 18 June 2022. https://www.practicalpainmanagement.com/news/research-update-mdma-and-psilocybin-for-pain-management Accessed 31 July 2023. Fanciullacci M, et al. “Brief report: phantom limb pain: sub-hallucinogenic treatment with lysergic acid diethylamide (LSD).” Headache. 1977 July; 17(3): 118-119. https://pubmed.ncbi.nlm.nih.gov/893080/ Accessed 30 July 2023Flanagan T, Nichols C. “Psychedelics as anti-inflammatory agents.” Psychedelic Research. 13 Aug 2018. Accessed 28 July 2023. https://blossomanalysis.com/papers/psychedelics-as-anti-inflammatory-agents/Hawryluk M. “Pain, hope, and science collide as athletes turn to magic mushrooms.” WUSF Public Media. 30 Apr 2023. https://wusfnews.wusf.usf.edu/health-news-florida/2023-04-30/pain-hope-and-science-collide-as-athletes-turn-to-magic-mushrooms Accessed 30 July 2023. Kooijman NI, et al. “Are psychedelics the answer to chronic pain: A review of current literature.” Pain Pract. 2023 Apr;23(4):447-458. Accessed 30 July 2023. doi: 10.1111/papr.13203. Epub 2023 Jan 11. PMID: 36597700.“Lobe Sciences announces launch of pre-clinical study in collaboration with the University of Miami Miller School of Medicine.” Newsfile. 30 Nov 2020. Accessed 27 July 2023. https://www.newsfilecorp.com/release/69106/Lobe-Sciences-Announces-Launch-of-Preclinical-Study-in-Collaboration-with-the-University-of-Miami-Miller-School-of-MedicineMade, Rachel. “Jim Harris was paralyzed. Then he ate magic mushrooms.” Outside. 9 Nov 2022. Accessed 27 July 2023. https://www.outsideonline.com/outdoor-adventure/exploration-survival/psychedelics-research-paralysis-treatment-jim-harris/Mansoor Khan S, et al. “Psychedelics for brain injury: a mini review.” Frontiers in Neurology. 2021(12). 29 July 2021. Accessed 28 July 2023. https://www.frontiersin.org/articles/10.3389/fneur.2021.685085/fullPrice S. “Data shows combination psilocybin therapy effective for TBI and PTSD.” Psychedelic Health UK. 30 Sept 2021. Accessed 30 July 2023. https://psychedelichealth.co.uk/2021/09/30/data-shows-combination-psilocybin-therapy-effective-for-tbi-and-ptsd/Rauchman B. “UFC fighter’s brain injury successfully treated with psychedelic therapy.” Pacific Neuroscience Institute. 6 July 2023. Accessed 28 July 2023. https://www.pacificneuroscienceinstitute.org/blog/trip/ufc-fighters-brain-injury-successfully-treated-with-psychedelic-therapy/Ramachandran V, et al. “Relief from intractable phantom pain by combining psilocybin and mirror visual feedback (MVF).” Neurocase. 2018 Apr; 24(2): 105-110. Accessed 29 July 2023. https://pubmed.ncbi.nlm.nih.gov/29764303/Rosenhall U, et al. “Treatment of military acoustic accidents with n-acetyl-l-cysteine (NAC). Int J Audiology. 2019 March; 58(3): 151-157. Accessed 30 July 2023. https://pubmed.ncbi.nlm.nih.gov/30653365/Schindler et al. “Exploratory investigation of a patient informed low dose psilocybin pulse regimen in the suppression of cluster headaches: results from a randomized, double-blind, placebo-controlled trial.” Headache. 23 Nov 2022. https://headachejournal.onlinelibrary.wiley.com/doi/abs/10.1111/head.14420 Accessed 30 July 2023. “Traumatic Brain Injury and Concussion.” Centers for Disease Control. Last Reviewed: 7 July 2023. Last access 29 July 2023. https://www.cdc.gov/traumaticbraininjury/data/index.html Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

George Sellhorn Ph.D, is the founder, owner and Principal Scientist of Flourish Labs in Portland Oregon and earned his Ph.D. in Molecular Plant Sciences from Washington State University (2006) and his B.S. in Biology from Indiana University (1999). George has worked in both academia and the biotechnology industries from 2006-2021 working on projects such as HIV vaccine development, production, characterization and pre-clinical evaluation as well as bioconjugate-based therapeutics including pegylated interferon for multiple sclerosis, bifunctional antibodies and antibody drug conjugates for breast cancer and poly(carboxybetaine) L-asparaginase bioconjugates for acute lymphoblastic leukemia.George has 23 years of extensive experience with liquid chromatography using both High-Performance Liquid Chromatography (HPLC) and Fast protein liquid chromatography (FPLC) and these techniques are one of his primary expertise. Some of the leadership roles he has held in the laboratory include Senior Scientist, Laboratory Director and Principal Investigator. George has also worked in the medical and recreational Cannabis industries from 2009-2021 which included cultivation, processing and consulting in Washington, Oregon and Colorado. Flourish Labs, LLC was founded in August 2021 and opened its services to customers on January 1st , 2022.Link to George’s business here at Flourish Labs (OR): https://flourishlabsoregon.com/Glossary of termsAPE—Albino Penis Envy, considered one of the most potent strains of psilocybin cubensis in terms 4-ACO: Or O-acetylpsilocybin or 4-Aco-DMT: semi synthetic derivatives of psilocybin often used in pharmacologic studiesBOL or 2-Br-LSD. Non hallucinogenic LSD derivative synthesized by Albert Hofman (who also synthesized LSD). CLIA and CAP: College of American pathologists and Clinical Laboratory Improvement Amendments—regulatory bodies for clinical laboratories. COA-certificate of analysis, offered by third party product testing labs. CRM: Certified Reference Materials (not Customer Relationship Management in this context)Entourage effect: hypothesis that compounds in cannabis other than CBD and THC act in synergy to exhibit pharmacologic effect (pretty good evidence to support this). GPCR: G protein coupled receptor: largest family of membrane proteins LOQ—Limit of quantification LOD—Level of detection. Level of detection is smallest concentration of a sample that can be consistently analyzed with 95% probability, LOQ is smallest concentration that can be measured with less than 10 to 20% variation. PSK (Krestin): Also known as Polysaccharide K, derived from Coriolus versicolor mushroom, widely used as folk remedy and adjuvant therapy for cancer treatment in some cultures. Terpenoids: Broad class of naturally occurring 5 Carbon molecules that show wide range of pharmacologic activities. 5-ME-O-DMT: Psychoactive drug derived from toad venom of glands of the Sonoran Desert toad (lots more to come on this). Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Notes: Per Christopher Toney, a reminder that psilocybin dosing is based on dry weight of the whole mushrooms, for those curious about how dosing is calculated. How well does this approximate actual psilocybin content? This will be a good future topic for discussion. References:Link to FDA’s Considerations for Clinical Investigations of Psychedelic Drugs (Accessed 11 July 2023): https://www.fda.gov/regulatory-information/search-fda-guidance-documents/psychedelic-drugs-considerations-clinical-investigations. Bogenschutz MP, et al. Percentage of heavy drinking days following psilocybin assisted psychotherapy vs placebo in the treatment of patients with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2022; 79(10): 953-962 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2795625Carhart-Harris R, et al. Trial of psilocybin versus escitalopram for depression. New England Journal of Medicine. 2021: 384: 1402-1411. https://www.nejm.org/doi/full/10.1056/nejmoa2032994Ebbesen-Jensen M, et al. Psilocybin assisted therapy for reducing alcohol intake in patients with alcohol use disorder: protocol for a randomized, double blinded, placebo controlled 12 week clinical trial (the QUANTUM trip trial). BMJ Open. 2022; 12(10). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577917/Ercolano, A. (2023) Johns Hopkins Center for psychedelic and Consciousness Research, Johns Hopkins Medicine. Available at: https://www.hopkinsmedicine.org/psychiatry/research/psychedelics-research.html Fauber J and Fiore K. Slippery slope: Fen-Phen users recall a “miracle” turned nightmare. Milwaukee Journal Sentinel/Med Page Today. 19 April 2015. https://www.medpagetoday.com/special-reports/slipperyslope/51044Goodwin GM, et al. Single dose psilocybin for treatment for a treatment resistant episode of major depression. New England Journal of Medicine. 2022; 387(18). https://www.nejm.org/doi/pdf/10.1056/NEJMoa2206443?articleTools=true Griffiths RR, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double blind trial. Journal of Psychopharmacology. 2016; 30(2): 1181-1197Grob CS, et al. Pilot study of psilocybin for anxiety in patients with advanced stage cancer. JAMA Psychiatry. 2011; 68(1): 71-78. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/210962Kenney A. What to know about Colorado’s psychedelic law. Colorado Public Radio. 21 June 2023. https://www.cpr.org/2023/06/21/colorado-psychedelic-law-for-psilocybin-mushrooms/Rosenbaum D, et al. Psychedelics for existential distress in palliative and cancer care. Current Oncology. 2019; 26(4): 225-226. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726261/Ross S, et al. Acute and sustained reductions in loss of meaning and suicidal ideation following psilocybin-assisted psychotherapy for psychiatric and existential distress in life threatening cancer. ACS Pharmacology and Translational Science. 2021; 4(2): 553-562. https://pubmed.ncbi.nlm.nih.gov/33860185/Rotz VR, et al. Single dose psilocybin assisted therapy in major depressive disorder: a placebo controlled, randomized double blind trial. The Lancet. 2023;56: 101809. https://www.thelancet.com/action/showPdf?pii=S2589-5370%2822%2900538-7To read about “Mad Honey” that we referenced towards the end of the podcast: see here: https://bigthink.com/health/mad-honey/#:~:text=But%20what%20really%20distinguishes%20mad,%2C%20in%20rare%20cases%2C%20death. Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

References:Gotvaldova K, et al. "Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids". International Journal of Molecular Sciences. 2023 (22): 14068.Halpern J, Roth BL "Hallucinogens and dissociative agents naturally growing in the United States". Pharmacology & Therapeutics. 2004; 102 (2): 131–8.Huberman A. The science of MDMA and its therapeutic uses: benefits and risks. Huberman Labs (podcast). 12 Jun 2023Pollan M. How to change your mind: the new science of psychedelics. Penguin Press. 2019Sumner R, et al. Microdosed LSD: Dose day outcomes from a home-administered randomized controlled trial. 2023. Unpublished (information from poster presentation at MAPS conference)Woolley DW, Campbell NK (1962). "Serotonin-like and antiserotonin properties of psilocybin and psilocin". Science. 3518. 136 (3518): 777–8Vizeli P, et al. Genetic influence of Cyp2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis. Scientific Reports. 2021(11); 10851. Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

***Disclaimer: this podcast is intended for informational purposes only on the safety and efficacy data of the substances discussed. As healthcare professionals, we do not advocate for or against the use of substances which are considered illicit by the United States Drug Enforcement Administration***References: Bonson KR, et al. Chronic administration of serotonergic anti-depressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology. 1996; 14(6)Gasser P, et al. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. The Journal of Nervous and Mental Disease. 2014; 202(7): 513-520Lopez-Gimenez JF, Gonzalez-Maeso J. Hallucinogens and Serotonin 5HT2A Receptor Mediated Signaling Pathways. Current Topics in Behavioral Neuroscience. 2018; 36: 45-73Liechti ME. Modern Clinical Research on LSD. Neuropsychopharmacology. 2017; 42: 2114-2127.Murphy RJ, et al. MDLSD: study protocol for a randomised, double-masked, placebo-controlled trial of repeated microdoses of LSD in healthy volunteers. Trials. 2021; 22. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05243-3Murphy RJ, et al. Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Biological Psychiatry. 28 March 2023. https://www.biologicalpsychiatryjournal.com/article/S0006-3223(23)01164-2/fulltext#gr2Passie T, et al. The pharmacology of lysergic acid diethylamide: a review. CNS Neuroscience and Therapeutics. 11 Nov 2018. https://onlinelibrary.wiley.com/doi/10.1111/j.1755-5949.2008.00059.x Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Audio Correction: Colby misspoke 4:15: meant to say “Methergine is used for postpartum hemorrhage after delivery,” said “hemorrhage after bleeding” (which of course is redundant and a mistake). Article on Ergotamine association with the Salem Witch Trials (from the Outside Hustle, Colby’s other blog): Blotter Art examples: https://keseyblotterart.com/References: Bryant C, Clark J. “How LSD Works.” Stuff You Should Know [podcast] 5 May 2016. Dyck E. LSD: a new treatment emerging from the past. CMAJ. 2015 Aug 4;187(14):1079–80. doi: 10.1503/cmaj.141358. Epub ahead of print. PMID: 26243813; PMCID: PMC4592308.Dyck, E. (2006). ‘Hitting Highs at Rock Bottom’: LSD Treatment for Alcoholism, 1950–1970. Soc. Hist. Med. 19: 313-329. [PDF]Gasser, P. et al. (2014). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. J. Nerv. Ment. Dis. 202: 513-520. [Full text]Irwin, S. A., et al. (2013). Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial. J. Palliat. Med. 16: 958-965. [PDF]Pollen M. “How to Change Your Mind: What the New Science of Psychedelics Teaches us About Consciousness, Dying, Addiction, Depression, and Transcendence.” Penguin Press. New York. 2018. Sandison, R. A., et al. (1954). The therapeutic value of lysergic acid diethylamide in mental illness. J. Ment. Sci. 100: 491-507. [Summary]Sandison, R. A. & Whitelaw, J. D. A. (1957). Further studies of the therapeutic value of lysergic acid diethylamide in mental illness. J. Ment. Sci. 103: 332-343. [Summary]Sessa, B. (2008). Can psychedelic drugs play a role in palliative care? Eur. J. Pall. Care 15: 235-237. [PDF]Simmons, J. Q., et al. (1966). Modification of Autistic Behavior with LSD-25. Am. J. Psych. 122: 1201-1211. [Summary]Smart, R. G. & Storm, T. (1964). The Efficacy of LSD in the Treatment of Alcoholism. Quart. J. Alcohol 25: 333-338. [PDF]Smith, C. M. (1958). A New Adjunct to the Treatment of Alcoholism: The Hallucinogenic Drugs. Quart. J. Alcohol 19: 406-417. [PDF]Shroder T. “Apparently Useless: The Accidental Discovery of LSD. The Atlantic. 9 Sept 2014. Available at: https://www.theatlantic.com/health/archive/2014/09/the-accidental-discovery-of-lsd/379564/Tanne, J. H. (2004). Humphrey Osmond. BMJ 328: 713. [Full text]Vollenweider F. X. & Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Rev. Neurosci. 11: 642-651. [PDF] Get full access to Neural Pharm at neuralpharm.substack.com/subscribe

Introducing the Neural Pharm Podcast, featuring your hosts Colby Burns, PharmD, and Christopher Toney, PharmD. Episode 1 establishes the mission of the podcast, and covers the groundbreaking MAPP1 and MAPP2 trials that established MDMA as a breakthrough therapy for PTSD. We also cover key safety data including drug interactions, pharmacokinetics (or metabolism), and pharmacogenomics (or gene-drug interactions). Come join us! ***Correction Alert: The Ted talk referenced by Colby in the conclusion of the podcast was given by Dr. Ben Sessa, not Sassa (see the attached video in the reference section)****References: * Mitchell J, et al. MDMA Assisted Therapy for Severe PTSD: A randomized, double blind, placebo controlled phase 3 study. Nature. 10 May 2021 https://www.nature.com/articles/s41591-021-01336-3>* Mental Health By the Numbers. National Alliance on Mental Illness. 2023. * Sessa B, et al. A Review of 3,4-methylenedioxymethamphetamine (MDMA) Assisted Psychotherapy. 2019(10). * Sessa B. Is MDMA psychiatry’s antibiotic? Tedx University of Bristol. 5 July 2016. See video below. * Silverstone P. The Promise of Psychedelics: Science Based Hope for Better Mental Health. 2022 Apr 21. Ingenium books. Referenced in podcast to be discussed in future episode:Christie D, Kryskow P. MDMA Assisted Psychotherapy for Fibromyalgia and Other Centralization Syndromes. Psychedelics Today (podcast). 21 Feb 2023 Get full access to Neural Pharm at neuralpharm.substack.com/subscribe